Epigenetic Regulation of miR-129-2 Leads to Overexpression of PDGFRa and FoxP1 in Glioma Cells

  • Tian, Xiang-Yang (Department of Neurosurgery, Xinxiang Central Hospital) ;
  • Zhang, Ling (Medical Record Office, Xinxiang Central Hospital) ;
  • Sun, Lai-Guang (Department of Neurosurgery, Xinxiang Central Hospital) ;
  • Li, Ming (Experimental Center, the Second Affiliated Hospital of Soochow University)
  • Published : 2015.09.02


miR-129-2 is frequently downregulated in multiple cancers. However, how it is silenced in cancers remains unclear. Here we investigated the expression profile and potential biological function of miR-129-2 in glioblastoma (GBM), the most common and lethal form of brain tumors in adults. We showed that miR-129-2 is lost in GBM patient specimens and cultured cell lines. miR-129-2 expression could be restored upon treatment with a histone deadetylase inhibitor (trichostatin A) but not a DNA methylation inhibitor (5-Aza-2'-deoxycytidine), and more profound effect was observed with the treatment of these two drugs in combination. Furthermore, forced expression of miR-129-2 repressed the expression of major oncogenic genes such as PDGFRa and Foxp1 in GBMs. Consistently, expression of miR-129-2 significantly inhibits GBM cell proliferation in vitro. These results reveal that miR-129-2 is epigenetically regulated and functions as a tumor suppressor gene in GBMs, suggesting it may serve as a potential therapeutic target for GBM treatment.


  1. Calin GA, Croce CM (2006). MicroRNA signatures in human cancers. Nat Rev Cancer, 6, 857-66.
  2. Chen X, Zhang L, Zhang T, et al (2006). Methylation-mediated repression of microRNA 129-2 enhances oncogenic SOX4 expression in HCC. Liver Int, 3, 476-86.
  3. Dossing KB, BinderuP T, Kaczkowski B, et al (2014). Down-Regulation of miR-129-5p and the let-7 Family in Neuroendocrine Tumors and Metastases Leads to Up- Regulation of Their Targets Egr1, G3bp1, Hmga2 and Bach1. Genes (Basel), 6, 1-21
  4. Fesler A, Zhai H, Ju J (2014). miR-129 as a novel therapeutic target and biomarker in gastrointestinal cancer. Onco Targets Ther, 7, 1481-5.
  5. Floyd D, Purow B (2014). Micro-masters of glioblastoma biology and therapy: increasingly recognized roles for microRNAs. Neuro Oncol, 16, 622-7.
  6. Furnari FB, Cloughesy TF, Cavenee WK, et al (2015). Heterogeneity of epidermal growth factor receptor signalling networks in glioblastoma. Nat Rev Cancer, 15, 302-10.
  7. Gregory RI, Yan KP, Amuthan G, et al (2014). The Microprocessor complex mediates the genesis of microRNAs. Nature, 432, 235-40.
  8. Gomez GG, Volinia S, Croce CM, et al (2014). Suppression of microRNA-9 by mutant EGFR signaling upregulates FOXP1 to enhance glioblastoma tumorigenicity. Cancer Res, 74, 1429-39.
  9. Huang YW, Liu JC, Deatherage DE, et al (2009). Epigenetic repression of microRNA-129-2 leads to overexpression of SOX4 oncogene in endometrial cancer. Cancer Res, 69, 9038-46.
  10. Karaayvaz M, Zhai H, Ju J. (2013). miR-129 promotes apoptosis and enhances chemosensitivity to 5-fluorouracil in colorectal cancer. Cell Death Dis, 4, 659.
  11. Li M, Mukasa A, Inda MM, et al (2011). Guanylate binding protein 1 is a novel effector of EGFR-driven invasion in glioblastoma. J Exp Med, 208, 2657-73.
  12. Li M, Tian L, Wang L, et al (2013). Down-regulation of miR- 129-5p inhibits growth and induces apoptosis in laryngeal squamous cell carcinoma by targeting APC. PLoS One, 8, 77829.
  13. Liu KW, Hu B, Cheng SY (2011). Platelet-derived growth factor receptor alpha in glioma: a bad seed. Chin J Cancer, 30, 590-602.
  14. Liu MX, Zhou KC, Cao Y. MCRS1 overexpression, which is specifically inhibited by miR-129*, promotes the epithelialmesenchymal transition and metastasis in non-small cell lung cancer. Mol Cancer, 13, 245.
  15. Lu CY, Lin KY, Tien MT, et al (2013). Frequent DNA methylation of MiR-129-2 and its potential clinical implication in hepatocellular carcinoma. Genes Chromosomes Cancer, 52, 636-43.
  16. Ma L, Young J, Prabhala H, Pan E, et al (2010). miR-9, a MYC/ MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol, 12, 247-56.
  17. Wu J, Qian J, Li C, et al (2010). miR-129 regulates cell proliferation by downregulating Cdk6 expression. Cell Cycle, 9, 1809-18.
  18. Zhang J, Li S, Yan Q, et al (2013). Interferon-${\beta}$ induced microRNA-129-5p down-regulates HPV-18 E6 and E7 viral gene expression by targeting SP1 in cervical cancer cells. PLoS One, 8, 81366.

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